It has previously been shown that immune response genes (Ir genes) which map within the major histocompatibility complex (H-2) of mice determine the ability of various inbred strains of mice to respond to diverse antigens with antibody production and/or cellular immunity. It as previously been shown by some of the present investigators that the immune response to the natural protein antigen, staphylococcal nuclease (henceforth "Nase"), whose structure has been well studied, is under H-2-linked Ir-gene control. This response is being investigated from two different points of view: 1) By studying the relative proportions of antibodies to different antigenic determinants on Nase made under Ir-gene control by high responder and low responder strains, and 2) by studying the immune response in appropriately chosen strains to polypeptide fragments of Nase each bearing only one or a few of the several antigenic determinants on the whole Nase molecule.